Project Summary - Abstract The Metabolism Core is designed to conduct in vivo and physiological experiments in conscious mice for the purpose of detailed metabolic phenotyping of transgenic mouse models useful in understanding obesity, diabetes and its complications. The Core operates under the supervision of Dr. Jason Kim (Director) and Drs. Roger Davis and Hye-Lim Noh as co-Directors who oversee day-to-day operation of the Core and interact with the users of the UMass MMPC. The principal functions of the Core are to perform the following experiments: 1) hyperinsulinemic-euglycemic clamp to assess organ-specific insulin action and glucose metabolism in conscious mice, 2) hyperglycemic clamp to assess in vivo pancreatic ?-cell function in conscious mice, 3) glucose/insulin tolerance tests, 4) survival surgery for in vivo experiments, 5) implementation of osmotic pumps for chronic delivery of drugs or other agents, 6) application of special diet (e.g., high-fat diet) to alter energy balance and induce obesity in mice, 7) acute lipid infusion, acute/chronic delivery of cytokines, and STZ injection to alter glucose homeostasis, 8) non-invasive measurement of energy expenditure, respiratory exchange ratio, physical activity, and food/water intake in conscious mice using metabolic cages, 9) non-invasive assessment of whole body, organ, and tissue biopsy composition of fat/lean/water mass in conscious mice using 1H-MRS, 10) implementation of treadmill and cage wheels for exercise study, 12) biochemical analysis for intracellular metabolic flux measurement (glycolysis, glycogen synthesis), and 13) blinded drug trial studies. The Metabolism Core regularly interacts with the Analytical and Functional Core for complementary, high-throughput analytical assays to measure hormones, cytokines and metabolites using serum samples obtained at the end of metabolic experiments. The goal of the Metabolism Core is to use an array of elegant, non-invasive and in vivo experiments to obtain a robust set of metabolic data from individual mouse in order to provide mechanistic insights into the role of selected gene on obesity, insulin resistance, and diabetes.